Anticoagulant peptide aldehyde derivatives

Abstract

This invention relates to peptide aldehyde derivatives of formula (I): D-Xaa-Pro-Arg-H, wherein Xaa represent a 2-cycloheptyl-2-hydroxyacetyl or 2-cyclopentyl-2-hydroxyacetyl group, Pro represents an L-prolyl residue and Arg represents an L-arginyl residue, their acid-additon salts formed with an organic or inorganic acid and pharmaceutical compositions containing the same. The compounds of formula (I) of the invention have therapeutic, particularly anticoagulant, antiplatelet and antithrombotic properties.

What we claim is: 
     
       1. A compound of formula (I),   D-Xaa-Pro-Arg-H                                            (I)     wherein   Xaa represents a 2-cycloheptyl-2-hydroxyacetyl or 2-cyclopentyl-2-hydroxyacetyl group,   Pro represents an L-prolyl residue and   Arg represents an L-arginyl residue,   or an acid-addition salt thereof formed with an organic or inorganic acid.   
     
     
       2. D-2-Cycloheptyl-2-hydroxyacetyl-L-prolyl-L-arginine aldehyde and its acid-addition salts. 
     
     
       3. D-2-Cycloheptyl-2-hydroxyacetyl-L-prolyl-L-arginine aldehyde hemisulfate. 
     
     
       4. D-2-Cyclopentyl-2-hydroxyacetyl-L-prolyl-L-arginine aldehyde and its acid-addition salts. 
     
     
       5. D-2-cyclopentyl-2-hydroxyacetyl-L-prolyl-L-arginine aldehyde hemisulfate. 
     
     
       6. A pharmaceutical composition which comprises as active ingredient at least one compound of formula (I), wherein Xaa, Pro and Arg are as defined in claim 1, or a pharmaceutically acceptable acid-addition salt thereof in admixture with pharmaceutically acceptable solvents, diluents, carriers and/or additives. 
     
     
       7. A method of treating thrombosis and/or hypercoagulability-associated diseases, which method comprises administering to a mammal in need there of an effective amount of the formula (I) compound as defined in claim 1. 
     
     
       8. The method of claim 7, wherein the disease associated with thrombosis and/or hypercoagulability is selected from the group consisting of deep vein thrombosis, pulmonary embolism, arterial thrombosis, unstable angina, myocardial infarct, auricular fibrillation, stroke, coronary artery disease and thrombolic diseases of coronary arteries. 
     
     
       9. A method of preventing the reocclusion of arteries, which method comprises administering to a mammal in need there of an effective amount of compound of formula (I), as defined in claim 1.